Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10
Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused...
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| Veröffentlicht in: | Cellular and molecular life sciences : CMLS 2009-09, Vol.66 (18), p.3053-3065 |
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| creator | Dittmer, Angela Hohlfeld, Kristina Lützkendorf, Jana Müller, Lutz P Dittmer, Jürgen |
| description | Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell-cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell-cell adhesion and enhance migration of breast cancer cells by activating ADAM10. |
| doi_str_mv | 10.1007/s00018-009-0089-0 |
| format | Article |
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We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell-cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell-cell adhesion and enhance migration of breast cancer cells by activating ADAM10.</description><identifier>ISSN: 1420-682X</identifier><identifier>EISSN: 1420-9071</identifier><identifier>DOI: 10.1007/s00018-009-0089-0</identifier><identifier>PMID: 19603142</identifier><language>eng</language><publisher>Basel: Basel : SP Birkhäuser Verlag Basel</publisher><subject>Active Transport, Cell Nucleus ; ADAM Proteins - metabolism ; ADAM Proteins - physiology ; ADAM10 Protein ; Adhesion ; Amyloid Precursor Protein Secretases - metabolism ; Amyloid Precursor Protein Secretases - physiology ; Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Breast cancer ; Breast Neoplasms - pathology ; Cadherins - metabolism ; Cell Adhesion ; Cell adhesion & migration ; Cell Biology ; Cell Movement ; Coculture Techniques ; Humans ; Life Sciences ; Membrane Proteins - metabolism ; Membrane Proteins - physiology ; Mesenchymal Stem Cells - metabolism ; Mitogen-Activated Protein Kinase 3 ; Research Article ; Stem cells ; Studies ; Translocation ; Tumor Cells, Cultured</subject><ispartof>Cellular and molecular life sciences : CMLS, 2009-09, Vol.66 (18), p.3053-3065</ispartof><rights>Birkhäuser Verlag, Basel/Switzerland 2009</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c481t-6ecf70675a2b6ee8589ab433ecb57bb96a274ae443b5b829016833c09dfe2c063</citedby><cites>FETCH-LOGICAL-c481t-6ecf70675a2b6ee8589ab433ecb57bb96a274ae443b5b829016833c09dfe2c063</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115486/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11115486/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19603142$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Dittmer, Angela</creatorcontrib><creatorcontrib>Hohlfeld, Kristina</creatorcontrib><creatorcontrib>Lützkendorf, Jana</creatorcontrib><creatorcontrib>Müller, Lutz P</creatorcontrib><creatorcontrib>Dittmer, Jürgen</creatorcontrib><title>Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10</title><title>Cellular and molecular life sciences : CMLS</title><addtitle>Cell. Mol. Life Sci</addtitle><addtitle>Cell Mol Life Sci</addtitle><description>Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell-cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell-cell adhesion and enhance migration of breast cancer cells by activating ADAM10.</description><subject>Active Transport, Cell Nucleus</subject><subject>ADAM Proteins - metabolism</subject><subject>ADAM Proteins - physiology</subject><subject>ADAM10 Protein</subject><subject>Adhesion</subject><subject>Amyloid Precursor Protein Secretases - metabolism</subject><subject>Amyloid Precursor Protein Secretases - physiology</subject><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - pathology</subject><subject>Cadherins - metabolism</subject><subject>Cell Adhesion</subject><subject>Cell adhesion & migration</subject><subject>Cell Biology</subject><subject>Cell Movement</subject><subject>Coculture Techniques</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Membrane Proteins - metabolism</subject><subject>Membrane Proteins - physiology</subject><subject>Mesenchymal Stem Cells - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3</subject><subject>Research Article</subject><subject>Stem cells</subject><subject>Studies</subject><subject>Translocation</subject><subject>Tumor Cells, Cultured</subject><issn>1420-682X</issn><issn>1420-9071</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNp9kc1u1DAUhSMEoqXwAGzAYgGrwLUdO8kKjUqhSEUsoBI7y3ZuMq4m9tROKs3b4ygjCixqyT_S-e6xfU9RvKTwngLUHxIA0KYEaPNs8vKoOKUVg7KFmj4-nmXDfp0Uz1K6ybBomHxanNBWAs_qaTFezqP2ZMSE3m4Po96RNOFILO52iTjfzRbJRWl1t8XoPOlwiLrTkws-q8RE1GkiVkfrfBg1SfvMBdclYg5E28ndZdYPZPNp843C8-JJr3cJXxz3s-L688XP88vy6vuXr-ebq9JWDZ1KibavQdZCMyMRG9G02lScozWiNqaVmtWVxqriRpiGtUBlw7mFtuuRWZD8rPi4-u5nM2Jn0U9R79Q-ulHHgwraqX8V77ZqCHeK5iGqZnF4d3SI4XbGNKnRpaUp2mOYk6oz1ULLFvLtg6SsJedVJTL45j_wJszR5z4oRrmgggLNEF0hG0NKEfs_j6agltDVGrrKoasldAW55tXfv72vOKacAbYCKUt-wHh_80Our9eiXgelh-iSuv7B8hOXbjMKgv8GSDfBBw</recordid><startdate>20090901</startdate><enddate>20090901</enddate><creator>Dittmer, Angela</creator><creator>Hohlfeld, Kristina</creator><creator>Lützkendorf, Jana</creator><creator>Müller, Lutz P</creator><creator>Dittmer, Jürgen</creator><general>Basel : SP Birkhäuser Verlag Basel</general><general>SP Birkhäuser Verlag Basel</general><general>Springer Nature B.V</general><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SS</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>P64</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>RC3</scope><scope>7X8</scope><scope>7QO</scope><scope>5PM</scope></search><sort><creationdate>20090901</creationdate><title>Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10</title><author>Dittmer, Angela ; Hohlfeld, Kristina ; Lützkendorf, Jana ; Müller, Lutz P ; Dittmer, Jürgen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c481t-6ecf70675a2b6ee8589ab433ecb57bb96a274ae443b5b829016833c09dfe2c063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Active Transport, Cell Nucleus</topic><topic>ADAM Proteins - 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Mol. Life Sci</stitle><addtitle>Cell Mol Life Sci</addtitle><date>2009-09-01</date><risdate>2009</risdate><volume>66</volume><issue>18</issue><spage>3053</spage><epage>3065</epage><pages>3053-3065</pages><issn>1420-682X</issn><eissn>1420-9071</eissn><abstract>Mesenchymal stem cells (MSCs) have been shown to communicate with tumor cells. We analyzed the effect of human MSCs (hMSCs) on breast cancer cells in three-dimensional cultures. By using GFP expression and immunohistochemistry, we show that hMSCs invade 3D breast cancer cell aggregates. hMSCs caused breast cancer spheroids to become disorganized which was accompanied by a disruption of cell-cell adhesion, E-cadherin cleavage, and nuclear translocation of E-cadherin, but not by epithelial/mesenchymal transition or by an increase in ERK1/2 activity. In addition, hMSCs enhanced the motility of breast cancer cells. Inhibition of ADAM10 (a disintegrin and metalloprotease 10), known to cleave E-cadherin, prevented both hMSC-mediated E-cadherin cleavage and enhanced migration. Our data suggest that hMSCs interfere with cell-cell adhesion and enhance migration of breast cancer cells by activating ADAM10.</abstract><cop>Basel</cop><pub>Basel : SP Birkhäuser Verlag Basel</pub><pmid>19603142</pmid><doi>10.1007/s00018-009-0089-0</doi><tpages>13</tpages></addata></record> |
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| subjects | Active Transport, Cell Nucleus ADAM Proteins - metabolism ADAM Proteins - physiology ADAM10 Protein Adhesion Amyloid Precursor Protein Secretases - metabolism Amyloid Precursor Protein Secretases - physiology Biochemistry Biomedical and Life Sciences Biomedicine Breast cancer Breast Neoplasms - pathology Cadherins - metabolism Cell Adhesion Cell adhesion & migration Cell Biology Cell Movement Coculture Techniques Humans Life Sciences Membrane Proteins - metabolism Membrane Proteins - physiology Mesenchymal Stem Cells - metabolism Mitogen-Activated Protein Kinase 3 Research Article Stem cells Studies Translocation Tumor Cells, Cultured |
| title | Human mesenchymal stem cells induce E-cadherin degradation in breast carcinoma spheroids by activating ADAM10 |
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